Category: Assay Development and Screening
Immunotherapy harnesses the power of the immune system to enhance and direct anti-tumor responses to treat cancer. Among the most promising and popular therapeutic approaches to activating anti-tumor immunity is through the blockade of immune checkpoints that are critical in regulating the degree and duration of immune system responses. One immune checkpoint of significance is the inhibitory trans-membrane protein cytotoxic T-Lymphocyte-associated protein 4 (CTLA-4 or CD152). CTLA-4 competes with CD28, a co-stimulatory and proinflammatory receptor also present on T-cells, for the same ligands (CD80 and CD86) on antigen presenting cells. CTLA-4 expression is upregulated with T-lymphocyte activation and interaction with its ligands results in downregulation of the immune response. The programmed cell death-1 (PD-1) immune checkpoint pathway is another negative regulator of T-cell immune function. Inhibitors that block PD-1 binding to its primary ligand, PD-L1 (programmed cell death-ligand 1), result in increased activation of T-cells and anti-tumor response. Currently, a handful of immune checkpoint drugs targeting the CTLA-4 and PD-1 immune checkpoint pathways have been approved by the FDA for the treatment of a variety of cancer types. The promise of therapeutically exploiting these immune checkpoints has created a need for more robust, straight-forward assays to identify novel drugs that inhibit and modulate these pathways. Amplified luminescence proximity homogeneous assay (Alpha) technology is a highly useful tool for the rapid screening of many potential drug candidates for novel immune checkpoint inhibitors. The assay protocols are extremely simple, require no wash steps, and are highly amenable to automation and miniaturization. We demonstrate in this poster how AlphaLISA® technology can be used to both detect and qualify inhibitors of two major immune checkpoint pathways and demonstrate both the selectivity and versatility of these assays.
Jeanine Hinterneder– Applications Scientist, PerkinElmer, Hopkinton, MA
Jeanine Hinterneder is an Applications Scientist in the Discovery Applications group at PerkinElmer. She received her Ph.D. from Brandeis University where her thesis work examined the mechanisms by which neurotrophic factors influence neuronal development. Jeanine has worked at PerkinElmer for the past 7 years primarily supporting the high throughput screening and microfluidic product lines. The goal of her research is to develop assays for novel targets and target classes and in vitro assays with increased biological relevance.